crossing96/oncoscreening huggingface dataset:
Integrative eQTL analysis of tumor and host omics data in individuals with bladder cancer.	Integrative analyses of several omics data are emerging. The data are usually generated from the same source material (i.e., tumor sample) representing one level of regulation. However, integrating different regulatory levels (i.e., blood) with those from tumor may also reveal important knowledge about the human genetic architecture. To model this multilevel structure, an integrative-expression quantitative trait loci (eQTL) analysis applying two-stage regression (2SR) was proposed. This approach first regressed tumor gene expression levels with tumor markers and the adjusted residuals from the previous model were then regressed with the germline genotypes measured in blood. Previously, we demonstrated that penalized regression methods in combination with a permutation-based MaxT method (Global-LASSO) is a promising tool to fix some of the challenges that high-throughput omics data analysis imposes. Here, we assessed whether Global-LASSO can also be applied when tumor and blood omics data are integrated. We further compared our strategy with two 2SR-approaches, one using multiple linear regression (2SR-MLR) and other using LASSO (2SR-LASSO). We applied the three models to integrate genomic, epigenomic, and transcriptomic data from tumor tissue with blood germline genotypes from 181 individuals with bladder cancer included in the TCGA Consortium. Global-LASSO provided a larger list of eQTLs than the 2SR methods, identified a previously reported eQTLs in prostate stem cell antigen (PSCA), and provided further clues on the complexity of APBEC3B loci, with a minimal false-positive rate not achieved by 2SR-MLR. It also represents an important contribution for omics integrative analysis because it is easy to apply and adaptable to any type of data.	bladder
Combining Protein and miRNA Quantification for Bladder Cancer Analysis.	We combine the telomerase extension reaction and microRNA (miRNA)-induced rolling circle amplification, followed by graphene oxide (GO) and nicking enzyme-assisted signal amplification as a method to analyze telomerase and miRNA-21 in urine samples with the following merits. First, it is a binary assay and can simultaneously output double signals that correspond to the quantities of telomerase and miRNA, respectively. Second, telomerase activity is enhanced by using a DNA molecular beacon probe to inhibit the formation of G-quadruplex. Third, background noise is decreased significantly via introduction of GO. Fourth, performance tests on about 258 urine samples demonstrate that this binary assay can distinguish between urine from bladder cancer patients, those with cystitis, and normal individuals. Finally, this strategy also shows great potential in distinguishing between muscle-invasive bladder cancers and non-muscle-invasive bladder cancers. The proposed strategy will greatly contribute to clinical decision-making and individualized treatments.	bladder
Improving Self-Efficacy and Self-Care in Adult Patients With a Urinary Diversion: A Pilot Study.	PURPOSE/OBJECTIVES: To evaluate the feasibility and acceptability of a multimodality educational intervention for improving self-efficacy (SE) and self-care in patients with a new urinary diversion (UD).	bladder
The Role of Robotics in the Invasive Management of Bladder Cancer.	Robot-assisted radical cystectomy (RARC) has been adopted widely in many centres, owed largely to the success of robot-assisted laparoscopic prostatectomy (RALP). It aims to replicate the oncological outcomes of open radical cystectomy (ORC), while providing a shorter recovery period. Despite this, previous RCTs have failed to show a benefit for RARC over ORC. These trials have compared extracorporeal RARC (eRARC) with ORC, which requires a further incision to mobilise the bowel for urinary reconstruction with an open technique. For intracorporeal RARC (iRARC), this urinary reconstruction is performed robotically without further incisions. There are theoretical benefits to this approach such as reduced recovery time for the bowel and reduced ileus rates, but no level 1 evidence currently exists to support this. While there has been an improvement in patient outcomes since the adoption of RARC, various other factors, such as enhanced recovery programmes and surgical learning curve, have made it difficult to attribute this solely to the robotic approach as many centres performing ORC have also shown similar improvements. In this review, we will discuss implementation of RARC as well as perioperative measures that have helped improve outcomes, offer a comparison of outcomes between ORC and RARC and highlight upcoming RCTs that may offer new evidence for or against a paradigm shift in the future of bladder cancer surgery.	bladder
Bladder cancer: oligometastases and imaging.	The term oligometastases was introduced to describe patients with limited metastatic disease in whom treatment might result in long-term disease-free survival or even cure. Imaging is pivotal for identification of these patients. The definition of oligometastatic bladder cancer and the optimal imaging modalities for diagnosis and response prediction remain to be determined.	bladder
Protein kinase C-α (PKCα) modulates cell apoptosis by stimulating nuclear translocation of NF-kappa-B p65 in urothelial cell carcinoma of the bladder.	BACKGROUND: The protein kinase C (PKC) family comprises central regulators of multiple signal transduction processes and is involved in the progression of many cancers. Nuclear factor Kappa-B (NF-κB) is constitutively expressed in cancer tissues and stimulates the transcription of various tumor-related genes. The present study aims to investigate the clinical significance of PKCα and NF-κB p65 in bladder cancer tissues and the mechanism underlying PKCα induction of bladder cancer cell apoptotic resistance through stimulation of p65 nuclear translocation. METHODS: Expression of PKCα and NF-κB subunit p65 was detected in seven bladder cancer cell lines by western blot and in 30 bladder cancer tissue specimens by immunostaining. Immunofluorescence was performed to evaluate p65 nuclear translocation induced by Phorbol 12-myristate 13-acetate (PMA). PKCα/β selective inhibitor Gö6976, PKC pan-inhibitor sotrastaurin, and the PKC siRNA were employed to conduct PKC inhibition/knockdown in bladder cancer cells. Luciferase reporter assays were performed to measure the activity of NF-κB. Flow cytometry and TUNEL analysis were used to assess cell apoptosis. RESULTS: Expression of PKCα and NF-κB was found to positively correlate with tumor progression in 30 tumor tissue specimens. Furthermore, a Pearson's correlation coefficient analysis revealed a positive correlation between PKCα and NF-κB expression. Among the PKC inhibitors, the PKCα/β selective inhibitor Gö6976 yielded the most significant block of PKCα and NF-κB activation by PMA. Knockdown of NF-κB p65 remarkably induced cell apoptosis, but PMA restored p65 expression and significantly suppressed cell apoptosis that was otherwise induced by the p65 knockdown alone. CONCLUSION: Our study showed that PKCα modulated cell resistance to apoptosis by stimulating NF-κB activation and thus promoted the tumorigenesis of bladder cancer.	bladder
The Efficacy of Trimodal Chemoradiotherapy with Cisplatin as a Bladder-Preserving Strategy for the Treatment of Muscle-Invasive Bladder Cancer.	INTRODUCTION: Open radical cystectomy (ORC) is currently the standard treatment for muscle-invasive bladder cancer (MIBC) without metastasis, while many patients with MIBC are not always appropriate candidates due to multiple comorbidities. To evaluate the bladder-preservation strategy, we compared the results with those obtained by ORC. PATIENTS AND METHODS: We retrospectively analyzed the data of 50 patients with MIBC treated by trimodal chemoradiotherapy with cisplatin (CDDP-radiation [CDDP-R]). Transurethral resection of the bladder tumor (TURBT) was performed before treatment to confirm pathological stage ≥T2. Extensive TURBT was performed after chemoradiotherapy to evaluate the pathological response to treatment. We compared the survival outcomes of our CDDP-R with those of ORC (retrospective cohort, n = 205) by propensity score matching analysis. RESULTS: The 2- and 5-year progression-free survival, bladder-intact survival, cancer-specific survival, and overall survival (OS) rates after treatment were 70.8 and 63.9%, 64.0 and 49.8%, 86.7 and 71.8%, and 84.3 and 64.8%, respectively. The 2- and 5-year OS rates after CDDP-R were 90.5 and 74.3%, respectively, and those after ORC were 71.8 and 59.9%, respectively, indicating a significant survival advantage conferred by CDDP-R over ORC (p < 0.05, HR 0.45, 95% CI 0.21-0.94). CONCLUSIONS: In selected patients, CDDP-R for MIBC may provide comparative oncological outcomes as ORC.	bladder
[THE MAIN STAGES OF THE PREPARATION OF VIABLE TUMOR CELLS OF BLADDER CANCER: FROM ISOLATION OF THE TUMOR MATERIAL TILL CRYOPRESERVATION OF CELL LINES].	The development of personalized autologous dendritic cell anti-tumor vaccines (PDPW) against bladder cancer (BC) is a relevant issue that covers many aspects required for its standardization. The article presents personal experimental studies related to development of optimal conditions of transportation of biological material; temperature and temporary modes for the storage of the samples; the materials about the optimal method of disaggregation of the biomaterial; there has been shown a comparative analysis of different methods of tumor disaggregation; the selection of nutritious growth mediums and growth factors for urothelial carcinoma cells (UCC), the conditions of cryopreservation of tumor cells for maximum UCC viability, potentially suitable for creating PDPW against BC.	bladder
Stromal antigen 2 functions as a tumor suppressor in bladder cancer cells.	Stromal antigen 2 (STAG2) is a subunit of the cohesion complex that plays an important role in the normal segregation of sister chromatids during mitosis or meiosis. However, the effect of STAG2 on the bladder cancer cell proliferation, migration, and invasion has not yet been fully clarified. In this study, we aimed to characterize STAG2 expression and functional significance in BC and adjacent normal tissue. Notably, STAG2 expression was markedly lower in BC cells and tumor tissues than their normal counterparts at the gene and protein levels. Moreover, clinicopathological analysis showed that the low STAG2 expression is associated with TNM stage. Functional analysis demonstrated that STAG2 overexpression attenuated cell proliferation via G1-phase arrest, invasion, and migration, and promoted apoptosis in BC cell lines, while the opposite was observed with STAG2 knockdown cells. Furthermore, STAG2 overexpression upregulated E-cadherin, caspase-3, and caspase-7 and downregulated vimentin, matrix metalloproteinase (MMP)2, and MMP9. Collectively, these data suggest that STAG2 acts as a tumor suppressor gene in bladder cancer and may be a potential therapeutic target in BC.	bladder
Challenges and advances in the diagnosis, biology, and treatment of urothelial upper tract and bladder carcinomas.	Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers.	bladder
Dose dense MVAC prior to radical cystectomy: a real-world experience.	PURPOSE: Our primary endpoint was to assess pathological response rate (pT0N0 and ≤pT1N0) for patients with BCa treated with the accelerated or dose dense MVAC (ddMVAC) chemotherapy followed by radical cystectomy (RC) in this real-word multi-institutional cohort. MATERIALS AND METHODS: We retrospectively reviewed records of patients with urothelial cancer who underwent ddMVAC and RC at seven contributing institutions from 2000 to 2015. Patients with cT2-4a, M0 BCa were included. Presence of cT3-4 disease, hydronephrosis, lymphovascular invasion and/or existence of sarcomatoid, or micropapillary features on the initial transurethral resection of bladder tumor specimen was defined as high-risk disease. Logistic regression models for prediction of pT0N0 and ≤pT1N0 were generated for the entire cohort as well as for the cN0 subgroup. The multivariable Cox proportional hazards regression model for survival using post RC data was used to assess hazard ratios (HRs) for the variables of interest. RESULTS: A total of 345 patients received ddMVAC chemotherapy during the study period; 85% had high-risk features. The median number of chemotherapy cycles was 4 (IQR 4-4); >90% of patients completed all scheduled cycles. The observed rates of pT0N0 and ≤pT1N0 were 30.4 and 49.3%, respectively, among cN0 patients. On the multivariable regression model, the presence of more than one clinical high-risk element was associated with 70% [OR 0.30 95% CI (0.10-0.86); p = 0.02] reduction in the odds of achieving partial pathological response. CONCLUSIONS: A complete response (pT0N0) was observed in one-third of patients after neoadjuvant ddMVAC therapy, and a partial response (≤pT1N0) was observed in nearly half of the cases in this real-world experience with this regimen. To our knowledge, this represents the largest experience outside clinical trial settings.	bladder
Prospective study comparing laparoscopic and open radical cystectomy: Surgical and oncological results.	INTRODUCTION: Laparoscopic radical cystectomy with lymphadenectomy and urinary diversion is an increasingly widespread operation. Studies are needed to support the oncological effectiveness and safety of this minimally invasive approach. PATIENTS AND METHODS: A nonrandomised, comparative prospective study between open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) was conducted in a university hospital. The main objective was to compare cancer-specific survival. The secondary objective was to compare the surgical results and complications according to the Clavien-Dindo scale. RESULTS: We treated 156 patients with high-grade invasive bladder cancer with either ORC (n=70) or LRC (n=86). The mean follow-up was 33.5±23.8 (range 12-96) months. The mean age was 66.9+9.4 years, and the male to female ratio was 19:1. Both groups were equivalent in age, stage, positive lymph nodes, in situ carcinoma, preoperative obstructive uropathy, adjuvant chemotherapy and type of urinary diversion. There were no differences between the groups in terms of cancer-specific survival (log-rank; P=.71). The histopathology stage was the only independent variable that predicted the prognosis. The hospital stay (P=.01) and operative transfusion rates (P=.002) were less for LRC. The duration of the surgery was greater for LRC (P<.001). There were no differences in the total complications rate (p=.62) or major complications (P=.69). The risk of evisceration (P=.02), surgical wound infection (P=.005) and pneumonia (P=.017) was greater for ORC. The risk of rectal lesion (P=.017) and urethrorectal fistulae (P=.065) was greater for LRC. CONCLUSION: LRC is an equivalent treatment to ORC in terms of oncological efficacy and is advantageous in terms of transfusion rates and hospital stays but not in terms of operating room time and overall safety. Studies are needed to better define the specific safety profile for each approach.	bladder
Impact of diagnostic ureteroscopy on intravesical recurrence in patients undergoing radical nephroureterectomy for upper tract urothelial cancer: a systematic review and meta-analysis.	Aim of this study was to analyse the association between the use of diagnostic ureteroscopy (URS) and the development of intravesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for high-risk upper tract urothelial carcinoma. A systematic review of the published data was performed up to December 2016, using multiple search engines to identify eligible studies. A formal meta-analysis was conducted of studies comparing patients who underwent URS before RNU with those who did not. Hazard ratios (HRs), with their 95% confidence intervals (CIs), from each study were used to calculate pooled HRs. Pooled estimates were calculated using a fixed-effects or random-effects model according to heterogeneity. Statistical analyses were performed using RevMan, version 5. Seven studies were included in the systematic review, but only six of these were deemed fully eligible for meta-analysis. Among the 2 382 patients included in the meta-analysis, 765 underwent diagnostic URS prior to RNU. All examined studies were retrospective, and the majority examined Asian populations. The IVR rate ranged from 39.2% to 60.7% and from 16.7% to 46% in patients with and without prior URS, respectively. In the pooled analysis, a statistically significant association was found between performance of URS prior to RNU and IVR (HR 1.56, 95% CI 1.33-1.88; P < 0.001). There was no heterogeneity in the observed outcomes, according to the I(2) statistic of 2% (P = 0.40). Within the intrinsic limitations of this type of analysis, these findings suggest a significant association between the use of diagnostic URS and higher risk of developing IVR after RNU. Further research in this area should be encouraged to further investigate the possible causality behind this association and it potential clinical implications.	bladder
Robot-assisted Laparoscopic Implantation of Brachytherapy Catheters in Bladder Cancer.	BACKGROUND: Robot-assisted laparoscopic (RAL) implantation of brachytherapy catheters (BTCs) can be a minimally invasive alternative to open retropubic implantation. Descriptions of the surgical technique and outcomes are sparse. OBJECTIVE: To describe our technique and perioperative outcomes for RAL BTC implantation in urothelial carcinoma (UC) and urachal carcinoma (UraC). DESIGN, SETTING AND PARTICIPANTS: Between June 2011 and May 2016, 26 patients with cN0M0 solitary T1G3 or T2G1-3 UC of ≤5cm or cN0M0 UraC were scheduled for external beam radiotherapy (20×2Gy), RAL BTC implantation, and pulsed-dose (29×1.04Gy) or high-dose rate brachytherapy (10×2.50Gy). Median follow-up was 12 mo (interquartile range 4-20). SURGICAL PROCEDURE: RAL BTC implantation with or without pelvic lymph node dissection and/or partial cystectomy. MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative data, complications, disease-free-survival (DFS), local recurrence-free survival (LRFS), and cystectomy-free survival (CFS) were evaluated as well as the feasibility of the technique. RESULTS AND LIMITATIONS: BTC implantation was successful in 92% of the patients. Median hospitalisation was 5 d (interquartile range 4-7) and blood loss <50ml in all cases. DFS was 74% at 1 yr and 63% at 2 yr. LRFS was 80% at 1 and 2 yr, and CFS was 87% at 1 and 2 yr. Early (≤30 d) high-grade complications (Clavien-Dindo ≥3) occurred in 8% of the patients. The study is limited by the small sample size and short follow-up time. CONCLUSIONS: RAL BTC implantation is technically feasible and could serve as safe, minimally invasive alternative to open surgery in selected patients. The results of this study should be confirmed in larger studies. PATIENT SUMMARY: Brachytherapy catheter (BTC) implantation is traditionally carried out via open retropubic surgery. We describe robot-assisted laparoscopic BTC implantation as a minimally invasive alternative. Perioperative outcomes are described and confirm the safety and feasibility of this procedure.	bladder
[Immunotherapy in urothelial carcinoma from a pathologist's perspective].	Immunotherapy with programmed cell death protein-1 (PD-1) antibodies (pembrolizumab and nivolumab) has been approved in Europe for the first-line treatment of several tumour entities, e. g. malignant melanoma. Following the resounding therapeutic success of these antibodies in different types of tumours, their potential in urological tumours has been investigated in several studies. The approval of the PD-1 antibody nivolumab for the treatment of metastasised renal cell carcinoma has set a new milestone in urooncology. This success continued with the approval of the programmed cell death ligand 1 (PD-L1) atezolizumab for advanced urothelial carcinoma in 2016. In addition, several ongoing clinical trials of other checkpoint inhibitors have also shown promising efficacy in advanced urothelial carcinoma. The decision to treat a patient with immunotherapy is based, among other things, on the immunohistochemical staining and evaluation by a pathologist. However, due to the lack of standardised evaluation protocols and detection systems, it is difficult to compare different studies and evaluate the efficacy of the respective antibodies.	bladder
Stenting Prior to Cystectomy is an Independent Risk Factor for Upper Urinary Tract Recurrence.	PURPOSE: Patients with bladder cancer who present with hydronephrosis may require drainage of the affected kidney before receiving further cancer treatment. Drainage can be done by retrograde stenting or percutaneously. However, retrograde stenting carries the risk of tumor cell spillage to the upper urinary tract. The aim of this study was to evaluate whether patients with bladder cancer are at higher risk for upper urinary tract recurrence if retrograde stenting has been performed prior to radical cystectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of 1,005 consecutive patients with bladder cancer who underwent radical cystectomy at our department between January 2000 and June 2016. Negative intraoperative ureteral margins were mandatory for study inclusion. Patients received regular followup according to our institutional protocol, including imaging of the upper urinary tract and urine cytology. RESULTS: Preoperative drainage of the upper urinary tract was performed in 114 of the 1,005 patients (11%), including in 53 (46%) by Double-J® stenting and in 61 (54%) by percutaneous nephrostomy. Recurrence developed in the upper urinary tract in 31 patients (3%) at a median of 17 months after cystectomy, including 7 of 53 (13%) in the Double-J group, 0% in the nephrostomy group and 24 of 891 (3%) in the no drainage group. Multivariate regression analysis revealed a higher risk of upper urinary tract recurrence if patients underwent Double-J stenting (HR 4.54, 95% CI 1.43-14.38, p = 0.01) and preoperative intravesical instillations (HR 2.94, 95% CI 1.40-6.16, p = 0.004). CONCLUSIONS: Patients who undergo Double-J stenting prior to radical cystectomy are at higher risk for upper urinary tract recurrence. If preoperative upper urinary tract drainage is required, percutaneous drainage might be recommended.	bladder